OBJECTIVE To analyze the specific risks and long-term toxicities of four BCR-ABL1 tyrosine kinase inhibitors （TKIs）（imatinib， dasatinib， nilotinib， and bosutinib） in pediatric patients with hematological malignancies. METHODS Adverse drug event （ADE） reports submitted to the the United States FDA Adverse Event Reporting System （FAERS） from January 2012 to December 2024， with imatinib， dasatinib， nilotinib， and bosutinib as the primary suspect drugs， were collected. Data mining was performed using the reporting odds ratio method and proportional reporting ratio method. ADE terms were classified and summarized by system organ class （SOC） and preferred term （PT） according to the Medical Dictionary for Drug Regulatory Activities （MedDRA， version 26.0）. Meanwhile， the ADE reports were divided by age into the adult group （≥18 years） and the pediatric group （＜18 years） to compare the differences in ADE between the two groups. RESULTS A total of 1 512 pediatric ADE reports were included： 993 for imatinib， 391 for dasatinib， 112 for nilotinib， and 16 for bosutinib. Among the reported ADEs， the patients were mainly aged 12-＜18 years； the reports mainly originated from the United States， France， and Japan； and the primary indications were chronic myeloid leukemia and acute lymphoblastic leukemia. A total of 5 256 ADE signals were mined， among which 235 were positive signals， involving 1 103 PT across 27 SOC. The top five PT ranked by the number of positive signals were nausea， febrile neutropenia， abdominal pain， neutropenia， and anemia. The top two SOC were general disorders and administration site conditions， and gastrointestinal disorders. Compared with the adult group， the pediatric group had relatively higher proportions of events related to infections and infestations as well as blood and lymphatic system disorders. Pediatric long-term toxicity signals primarily included growth retardation， accompanied by signals related to endocrine system abnormalities and bone metabolism abnormalities. Specific signals included imatinib-associated septic shock， dasatinib-associated chylothorax， and nilotinib-associated electrocardiographic QT interval prolongation. CONCLUSIONS When pediatric patients use BCR-ABL1 TKIs， priority monitoring of infection risk and hematologic parameters is required， along with long-term follow-up of height， endocrine， and bone metabolism parameters. Targeted screening and management of drug-specific signals should be performed to ensure the long-term safety of pediatric medication.

Background/Aims: Data from Asia regarding the short-term and long-term outcomes for acute severe ulcerative colitis (ASUC) are limited. We assessed the outcomes of ASUC, identified the risk factors for colectomy, and compared colectomy rates between the pre-biologics and post-biologics eras in Taiwan. Methods: The patients with an ASUC diagnosis between January 2013 and March 2022 at 5 tertiary medical centers were retrospectively analyzed. Results: In total, 98 patients were enrolled, with 68.4% diagnosed in the post-biologics era. In 78.6% of the ASUC patients initially received intravenous steroid therapy, for which the success rate was 74.1%. As for rescue therapy, 15 patients (93.8%) received biologics and 1 (6.3%) received cyclosporin. Biologics rescue therapy had a 93.3% success rate. One (1%) mortality due to septic shock occurred. The colectomy rate for index ASUC admission was 11.2%. Patients receiving colectomy were predominantly male (P= 0.012) and at older age (P= 0.016). Higher C-reactive protein (P= 0.035), lower albumin (P= 0.017), and hemoglobin (P= 0.023) levels were associated with colectomy risk. During a median follow-up of 24 months, 13 patients (15.1%) had recurrent ASUC and 23.1% of patients received colectomy. The accumulated colectomy rate at 3 years did not differ between the pre- and post-biologics eras (16.1% vs. 13.4%, P= 0.270). Conclusions This is the first Asian study on ASUC to compare colectomy rates between the prebiologics and post-biologics eras, revealing no significant difference. The recurrent ASUC had a higher colectomy rate than the index ASUC.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Objective To report the genetic analysis of a family with a fetus suspected of Ellis-van Creveld(EVC)syndrome based on ultrasound findings such as ventricular septal defect(VSD),short long bones in the limbs and polydactyly,and to conduct a literature review to clarify the pathogenic cause.Methods A 27-year-old pregnant woman,who was pregnant for the first time and had no prior deliveries,was admitted to the prenatal diagnosis center of Shijiazhuang Obstetrics and Gynecology Hospital in October 2021.At 17 weeks of gestation,ultrasound detected multiple fetal malformations.The genomic DNA of the fetal proband's amniotic fluid cells and the parents'peripheral blood samples were sequentially subjected to chromosomal karyotype analysis,chromosomal microarray analysis(CMA),and whole exome sequencing(WES).Suspected pathogenic mutations were verified by Sanger sequencing in the proband and its parents.Subsequently,a Minigene in vitro experiment was used to analyze one splicing mutation.Meanwhile,databases such as PubMed were searched,and literature reports were combined for genetic analysis.Results Chromosomal karyotype analysis of the fetus showed no abnormalities,and CMA did not detect any copy number variation(CNV)with clinical significance.WES results revealed two mutations in the EVC gene(NM_153717.2)of the fetus:a nonsense mutation c.1405G>T(p.E469X)in exon 10 and a splicing mutation c.1886+5G>A in intron 13.Family verification using Sanger sequencing showed that the father was a carrier of the c.1405G>T(p.E469X)mutation in exon 10,and the mother was a carrier of the c.1886+5G>A mutation in intron 13.The compound heterozygous mutation of the fetus was inherited from the parents.According to the guidelines of the American College of Medical Genetics and Genomics(ACMG)for classifying genetic variations,c.1405G>T(p.E469X)was classified as likely pathogenic mutation(PVS1+PM2),and c.1886+5G>A was classified as likely pathogenic mutation(PM2+PM3_Strong).The Minigene experiment results showed that the c.1886+5G>A mutation caused a 115-bp segment retention in intron 13,further supporting its pathogenicity.Review of the literature showed that the typical clinical manifestations of EVC syndrome include short limbs,short ribs,postaxial polydactyly,nail and tooth dysplasia,and congenital heart defects.Gene mutations in EVC/EVC2 were found to be the main pathogenic cause through whole exome sequencing,with mutation types including missense mutations,large-scale duplications/deletions,in-frame microdeletions,nonsense mutations,frameshift mutations,and splicing mutations.Conclusions The compound heterozygous mutations in the EVC gene are the pathogenic cause of the fetus.The detection of these mutations expands the genetic variation spectrum of Ellis-van Creveld syndrome.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Objective:To investigate the significance of urinary 8-oxo-7, 8-dihydroguanosine(8-oxoGuo)in assessing the short-term prognosis of sepsis in frail elderly patients.Methods:We conducted a cross-sectional study involving 62 frail elderly patients diagnosed with sepsis who were admitted to the Emergency Intensive Care Unit(EICU)at Beijing Hospital between March 2021 and March 2022.Based on their 28-day prognosis, the patients were categorized into two groups: those who died and those who survived.Upon admission, we collected urine samples and clinical data from both groups.We employed isotope dilution high-performance liquid chromatography-mass spectrometry to measure the levels of the RNA oxidation marker 8-oxoGuo in the urine.Results:A total of 62 frail elderly patients[aged(85.1±6.3)years]diagnosed with sepsis were included in the study, comprising 36 patients in the 28-day mortality group and 26 patients in the survival group.Univariate analysis revealed that the survival group had significantly lower body temperature, blood calcitonin(PCT)levels, sequential organ failure assessment(SOFA)scores, and urinary 8-oxoGuo levels compared to the mortality group.Additionally, the survival group exhibited a higher mean arterial pressure(MAP)than the mortality group, with all differences reaching statistical significance(all P<0.05).Spearman correlation analysis indicated that urinary 8-oxoGuo levels were positively correlated with both PCT and SOFA scores in frail elderly sepsis patients( r=0.426, 0.768, both P<0.05).Furthermore, logistic regression analysis identified urinary 8-oxoGuo and SOFA as independent risk factors for 28-day mortality in this population( OR=1.936, 1.427; P=0.006, 0.002).The area under the receiver operating characteristic curve(AUC)for urinary 8-oxoGuo and SOFA in predicting the 28-day prognosis of frail elderly sepsis patients was 0.761 and 0.741, respectively, both demonstrating statistical significance(both P<0.001). Conclusions:Our findings suggest that urinary 8-oxoGuo possesses strong predictive value for the short-term prognosis of sepsis in this vulnerable population.

Objective To observe the value of automated fiber quantification(AFQ)for analyzing relationships of abnormal white matter microstructures and executive dysfunction in children with attention deficit hyperactivity disorder(ADHD).Methods Brain diffusion tensor imaging(DTI)and white matter structure AFQ analysis were prospectively performed on 83 children with ADHD(ADHD group)and 52 healthy children(healthy control[HC]group).The axial diffusivity(AD),radial diffusivity(RD),mean diffusivity(MD),and fractional anisotropy(FA)of complete fiber bundles and respective segments were obtained and compared between groups.Partial correlation analysis was conducted of fiber bundle diffusion parameters and the scores of Swanson Nolan and Pelham-Ⅳ(SNAP-Ⅳ)and behavior rating inventory of executive function(BRIEF)in ADHD group.Receiver operating characteristic curves were applied to assess the efficacy of each diffusion parameter for evaluating ADHD.Results AD and MD of right anterior thalamic radiation(ATR),and AD of right cingulum bundle(CB)in ADHD group were all higher than those in HC group(FWE corrected,all P＜0.000 7).Significant differences of AD of the 54-78 segments of right ATR,MD of the 13-24 and 53-77 segments of right ATR,AD of the 24-26,53-56 and 93-97 segments of right CB,as well as MD of the 72-85 segments of left inferior longitudinal fasciculus(ILF)were found between groups(FWE corrected,all P＜0.001).In ADHD group,AD of 54-78 segments of right ATR were negatively correlated with the attention deficit scores,while of 24-26 segments of right CB were negatively correlated with the emotional control scores.MD of right ATR and some segments,AD of right CB and some segments in ADHD group were positively correlated with the scores of task initiation,planning,organization,monitoring and metacognitive index(all P＜0.05).The area under the curve(AUC)of segmental fiber bundle diffusion parameter and intact fiber bundle diffusion parameter for evaluating ADHD was 0.881 and 0.808,respectively,the former was higher than the latter(Z=2.435,P＜0.05).Conclusion AFQ could be used to analyze relationships of abnormal white matter microstructures and executive dysfunction in ADHD,which could be effectively evaluated based on specific fiber bundle segments.

IgA nephropathy is the most common primary glomerular disease globally, with the highest incidence in the Asian region, and has a high risk of progressing to end-stage renal disease even in patients with low proteinuria. The treatment paradigm for IgA nephropathy has undergone significant changes. Treatment should aim to reduce pathogenic IgA and IgA immune complex formation, including intestinal mucosal B cell immune modulators such as budesonide enteric-coated capsules, targeted APRIL and BAFF agents, and B cell depletors; it should also manage glomerular inflammation, including corticosteroids, mycophenolate mofetil, hydroxychloroquine, and targeting complement therapy; and it should manage general responses to nephron loss, including lifestyle interventions, renin-angiotensin system inhibitors, sodium-glucose cotransporter-2 inhibitors, and endothelin receptor antagonists. This article provides a comprehensive overview of the treatment paradigm and drug advancements for IgA nephropathy, aiming to provide more rational treatment options for IgA nephropathy patients and improve their outcomes.